What are the management and treatment options for Medication-Related Osteonecrosis of the Jaw (MRONJ)?

Management and Treatment Options for Medication-Related Osteonecrosis of the Jaw (MRONJ)

The initial approach to treatment of MRONJ should be conservative, including antimicrobial mouth rinses, antibiotics when clinically indicated, effective oral hygiene, and minor surgical interventions such as removal of superficial bone spicules. 1, 2

Diagnosis and Staging

Before initiating treatment, proper diagnosis and staging are essential:

Diagnostic Criteria

To establish a diagnosis of MRONJ, all three of the following must be present:

1. Current or previous treatment with a bone-modifying agent (BMA) or angiogenic inhibitor
2. Exposed bone or bone that can be probed through an intraoral/extraoral fistula in the maxillofacial region persisting for >8 weeks
3. No history of radiation therapy to the jaws or metastatic disease to the jaws 1

Staging System

Staging should be performed by a clinician experienced with MRONJ management 1:

Stage	Clinical Presentation	Treatment Strategy
At risk	No apparent necrotic bone	No treatment; patient education; reduce modifiable risk factors
Increased risk	No clinical evidence of necrotic bone but nonspecific findings	Symptomatic management; pain medication; dental specialist referral
Stage 1	Exposed/necrotic bone or fistulas; asymptomatic; no infection	Antibacterial mouth rinse; regular follow-up every 8 weeks
Stage 2	Exposed/necrotic bone or fistulas with infection, pain, erythema	Oral antibiotics; antibacterial rinse; pain control; debridement
Stage 3	Stage 2 plus: bone extending beyond alveolar bone, pathologic fracture, extraoral fistula, oroantral/oronasal communication	Antibiotics; pain control; surgical debridement/resection

Treatment Approach by Stage

Conservative Management (Initial Approach for All Stages)

• Antimicrobial mouth rinses (0.12% chlorhexidine)
• Antibiotics if clinically indicated (infection present)
• Pain management
• Effective oral hygiene maintenance
• Conservative removal of mobile sequestra without exposing uninvolved bone 1, 2

Stage-Specific Management

Stage 1 (Asymptomatic)

• Antibacterial mouth rinse
• Regular follow-up every 8 weeks by dental specialist
• Patient education and reduction of modifiable risk factors 1, 2

Stage 2 (Symptomatic with Infection)

• Oral antibiotics (penicillin, clindamycin, doxycycline, or first-generation cephalosporin)
• Topical antibacterial rinse
• Pain control
• Debridement to relieve soft tissue irritation and control infection
• Regular follow-up every 8 weeks 1, 2

Stage 3 (Advanced Disease)

• Oral antibiotics and topical antibacterial rinse
• Pain control
• Surgical debridement or resection for long-term palliation of infection and pain
• Regular follow-up every 8 weeks 1, 2

Surgical Approaches

Conservative Surgical Approach

• Removal of superficial bone spicules
• Extraction of symptomatic teeth within exposed necrotic bone (unlikely to exacerbate established necrotic process)
• Removal of mobile segments of bony sequestrum without exposing uninvolved bone 1

Aggressive Surgical Approach

• Reserved for refractory MRONJ that results in persistent symptoms or affects function despite initial conservative treatment
• May include mucosal flap elevation, block resection of necrotic bone, or soft tissue closure
• Not recommended for asymptomatic bone exposure
• Benefits and risks should be thoroughly discussed with the multidisciplinary care team and patient before proceeding 1, 3

Management of Patients on Bone-Modifying Agents (BMAs)

Continuation or Discontinuation of BMAs

• For patients diagnosed with MRONJ while on BMAs, there is insufficient evidence to support or refute discontinuation
• BMA administration may be deferred at the treating physician's discretion, in consultation with the patient and oral health provider
• For bisphosphonates: discontinuation may not affect outcomes due to long half-life
• For denosumab: temporary discontinuation may potentially enhance MRONJ resolution due to shorter half-life, but must be weighed against the risk of skeletal-related events 1, 2

Multidisciplinary Approach

A multidisciplinary team approach is crucial, including:

• Dentist/dental specialist
• Medical oncologist
• Maxillofacial surgeon

Regular communication between specialists about lesion status (resolved, improving, stable, or progressive) is essential, as the clinical course may affect treatment decisions regarding cessation or recommencement of BMAs 1, 2, 4

Prevention Strategies

Prevention is critical and includes:

1. Comprehensive oral evaluation before starting antiresorptive therapy
2. Dental care plan development and implementation before initiating BMA therapy
3. Addressing modifiable risk factors (poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes, tobacco use)
4. Avoiding elective dentoalveolar surgical procedures during active therapy with BMAs at oncologic doses
5. Regular dental follow-up (every 6 months) once BMA therapy has commenced 1, 2

Emerging Therapies

Some experimental approaches being investigated include:

• Bone marrow stem cell intralesional transplantation
• Low-level laser therapy
• Local platelet-derived growth factor application
• Hyperbaric oxygen
• Tissue grafting
• Teriparatide for enhanced osseous wound healing (in those without contraindications) 5

Common Pitfalls to Avoid

• Delayed diagnosis leading to disease progression
• Aggressive surgical intervention for asymptomatic cases
• Poor communication between specialists
• Ignoring modifiable risk factors
• Inadequate follow-up (recommended every 8 weeks until healing occurs) 2

By following these evidence-based guidelines and maintaining a conservative initial approach with escalation of treatment based on disease stage and response, clinicians can effectively manage MRONJ and improve quality of life for affected patients.